Identification and preliminary validation of biomarkers associated with mitochondrial and programmed cell death in pre-eclampsia
BackgroundThe involvement of mitochondrial and programmed cell death (mtPCD)–related genes in the pathogenesis of pre-eclampsia (PE) remains inadequately characterized.MethodsThis study explores the role of mtPCD genes in PE through bioinformatics and experimental approaches. Differentially expresse...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1453633/full |
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| author | Rong Lin Rong Lin XiaoYing Weng XiaoYing Weng Liang Lin Liang Lin XuYang Hu XuYang Hu ZhiYan Liu ZhiYan Liu Jing Zheng Jing Zheng FenFang Shen FenFang Shen Rui Li Rui Li |
| author_facet | Rong Lin Rong Lin XiaoYing Weng XiaoYing Weng Liang Lin Liang Lin XuYang Hu XuYang Hu ZhiYan Liu ZhiYan Liu Jing Zheng Jing Zheng FenFang Shen FenFang Shen Rui Li Rui Li |
| author_sort | Rong Lin |
| collection | DOAJ |
| description | BackgroundThe involvement of mitochondrial and programmed cell death (mtPCD)–related genes in the pathogenesis of pre-eclampsia (PE) remains inadequately characterized.MethodsThis study explores the role of mtPCD genes in PE through bioinformatics and experimental approaches. Differentially expressed mtPCD genes were identified as potential biomarkers from the GSE10588 and GSE98224 datasets and subsequently validated. Hub genes were determined using support vector machine, least absolute shrinkage and selection operator, and Boruta based on consistent expression profiles. Their performance was assessed through nomogram and artificial neural network models. Biomarkers were subjected to localization, functional annotation, regulatory network analysis, and drug prediction. Clinical validation was conducted via real-time quantitative polymerase chain reaction (RT-qPCR), immunofluorescence, and Western blot.ResultsFour genes [solute carrier family 25 member 5 (SLC25A5), acyl-CoA synthetase family member 2 (ACSF2), mitochondrial fission factor (MFF), and phorbol-12-myristate-13-acetate–induced protein 1 (PMAIP1)] were identified as biomarkers distinguishing PE from normal controls. Functional analysis indicated their involvement in various biological pathways. Immune analysis revealed associations between biomarkers and immune cell activity. A regulatory network was informed by biomarker expression and database predictions, in which KCNQ1OT1 modulates ACSF2 expression via hsa-miR-200b-3p. Drug predictions, including clodronic acid, were also proposed. Immunofluorescence, RT-qPCR, and Western blot confirmed reduced expression of SLC25A5, MFF, and PMAIP1 in PE, whereas ACSF2 was significantly upregulated.ConclusionThese four mtPCD-related biomarkers may play a pivotal role in PE pathogenesis, offering new perspectives on the disease’s diagnostic and mechanistic pathways. |
| format | Article |
| id | doaj-art-91411c0bccc44c8c97415041b96d4f6e |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-91411c0bccc44c8c97415041b96d4f6e2025-01-23T06:56:01ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.14536331453633Identification and preliminary validation of biomarkers associated with mitochondrial and programmed cell death in pre-eclampsiaRong Lin0Rong Lin1XiaoYing Weng2XiaoYing Weng3Liang Lin4Liang Lin5XuYang Hu6XuYang Hu7ZhiYan Liu8ZhiYan Liu9Jing Zheng10Jing Zheng11FenFang Shen12FenFang Shen13Rui Li14Rui Li15Medical Centre of Maternity and Child Health, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, ChinaFuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, ChinaMedical Centre of Maternity and Child Health, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, ChinaFuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, ChinaMedical Centre of Maternity and Child Health, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, ChinaFuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, ChinaMedical Centre of Maternity and Child Health, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, ChinaFuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, ChinaMedical Centre of Maternity and Child Health, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, ChinaFuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, ChinaMedical Centre of Maternity and Child Health, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, ChinaFuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, ChinaMedical Centre of Maternity and Child Health, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, ChinaFuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, ChinaMedical Centre of Maternity and Child Health, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, ChinaFuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, ChinaBackgroundThe involvement of mitochondrial and programmed cell death (mtPCD)–related genes in the pathogenesis of pre-eclampsia (PE) remains inadequately characterized.MethodsThis study explores the role of mtPCD genes in PE through bioinformatics and experimental approaches. Differentially expressed mtPCD genes were identified as potential biomarkers from the GSE10588 and GSE98224 datasets and subsequently validated. Hub genes were determined using support vector machine, least absolute shrinkage and selection operator, and Boruta based on consistent expression profiles. Their performance was assessed through nomogram and artificial neural network models. Biomarkers were subjected to localization, functional annotation, regulatory network analysis, and drug prediction. Clinical validation was conducted via real-time quantitative polymerase chain reaction (RT-qPCR), immunofluorescence, and Western blot.ResultsFour genes [solute carrier family 25 member 5 (SLC25A5), acyl-CoA synthetase family member 2 (ACSF2), mitochondrial fission factor (MFF), and phorbol-12-myristate-13-acetate–induced protein 1 (PMAIP1)] were identified as biomarkers distinguishing PE from normal controls. Functional analysis indicated their involvement in various biological pathways. Immune analysis revealed associations between biomarkers and immune cell activity. A regulatory network was informed by biomarker expression and database predictions, in which KCNQ1OT1 modulates ACSF2 expression via hsa-miR-200b-3p. Drug predictions, including clodronic acid, were also proposed. Immunofluorescence, RT-qPCR, and Western blot confirmed reduced expression of SLC25A5, MFF, and PMAIP1 in PE, whereas ACSF2 was significantly upregulated.ConclusionThese four mtPCD-related biomarkers may play a pivotal role in PE pathogenesis, offering new perspectives on the disease’s diagnostic and mechanistic pathways.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1453633/fullmitochondrialprogrammed cell deathpre-eclampsiabioinformaticsdatabase |
| spellingShingle | Rong Lin Rong Lin XiaoYing Weng XiaoYing Weng Liang Lin Liang Lin XuYang Hu XuYang Hu ZhiYan Liu ZhiYan Liu Jing Zheng Jing Zheng FenFang Shen FenFang Shen Rui Li Rui Li Identification and preliminary validation of biomarkers associated with mitochondrial and programmed cell death in pre-eclampsia Frontiers in Immunology mitochondrial programmed cell death pre-eclampsia bioinformatics database |
| title | Identification and preliminary validation of biomarkers associated with mitochondrial and programmed cell death in pre-eclampsia |
| title_full | Identification and preliminary validation of biomarkers associated with mitochondrial and programmed cell death in pre-eclampsia |
| title_fullStr | Identification and preliminary validation of biomarkers associated with mitochondrial and programmed cell death in pre-eclampsia |
| title_full_unstemmed | Identification and preliminary validation of biomarkers associated with mitochondrial and programmed cell death in pre-eclampsia |
| title_short | Identification and preliminary validation of biomarkers associated with mitochondrial and programmed cell death in pre-eclampsia |
| title_sort | identification and preliminary validation of biomarkers associated with mitochondrial and programmed cell death in pre eclampsia |
| topic | mitochondrial programmed cell death pre-eclampsia bioinformatics database |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1453633/full |
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